Method for producing hydroxy cyclammonium quaternary salts



Patented July 10, 1951 METHOD FOR PRODUCING HYDROXY CYCLAMMONIUMQUATERNARY SALTS Earl J. Van Lare and Leslie G. S. Brooker, Rochester,N. Y., assignors to Eastman Kodak Company, Rochester, N. Y., acorporation of New Jersey No Drawing. Application April 3, 1948, SerialNo. 18,846

8 Claims. 1

This invention relates to method for producing hydroxy cyclammoniumquaternary salts.

5-, 6-, 7- and 8-hydroxyquinaldine are known and these can be quatermzedby heating with an alkyl salt, e. g. dimethyl sulfate. However, in sucha process, the product is not pure hydroxyquinaldinemethornethylsulfate, owing to some methylation of the hydroxyl group.The same is true of hydroxylepidines andhydroxy-2,3,3-trimethylindolenines.

Kiprianov, Ushenko and Sych, J. Gen. Chem. U. S. S. R. 15, 200-206(1945), showed that 6- methoXy-2-methylbenzothiazole could be hydrolyzedwith concentrated hydrobromic acid or hydrochloric acid to give6-hydroxy-2-methylbenzothiazole hydrobromide or hydrochloride. Theyshowed that when 6-methoxy-2-methylbenzothiazole ethobromide washydrolyzed with hydrobromic acid, not only was the methoxyl grouphydrolyzed, but splitting out of alkyl halide took place, so that the6-hydroxy-2-methylbenzothiazole quaternary salt could not be obtained bysuch method. To obtain the quaternary salt of6-hydroXy-2-methylbenzothiazole, Kiprianov et al. were forced to resortto treating the hydrochloride of 6 hydroxy 2 methylbenzothiazole withethyl-p-toluenesulfonate which tends to contaminate the hydroxyquaternary salt owing to methylation of the hydroxyl group.

We have now found that unlike the ethobromide ofG-methoxy-Z-methylbenzothiazole, the alkobromides and the alkoiodides ofquinaldines and of lepidines containing an alkoxyl group in the 5-, 6-,7-- or 8-position, can be hydrolyzed, in hydrobromic acid, to give thecorresponding hydroxyl. quaternary salt, without the splitting out ofalkyl halide. Thus pure hydroxy quinaldine and lepidine quaternarysalts, free from contaminating alkoxyl derivatives, can be obtained. Welikewise'have been able to obtain pure hydroxy-2,3,3-trimethylindolenine quaternary salts and purehydroxynaphthothiazole quaternary salts in the same manner. In ourprocess, the alkobromide is obtained as the hydrolysis product and thiscan be converted to the alkiodide which, in turn, can be converted tothe alkochloride.

It is, accordingly, an object of our invention to provide new hydroxycyclammonium alkohalides. A further object is to provide a process forpreparing hydroxy cyclammonium quaternary salts free from contaminatingalkoxy cyclammonium quaternary salts. A still further object is toprovide new hydroxy dyes free from com taminating alkoxy dyes. Stillfurther objects will become apparent hereinafter.

. 2 In accordance with our invention, we provide hydroxy cyclammoniumquaternary salts which are free from contaminating alkoxy cyclammoniumquaternary salts by hydrolyzing, in hydrobromic acid, an alkoxycyclammonium alkobromide or alkiodide selected from those represented bythe following general formulas:

wherein It represents an alkyl group, especially a primary alkyl group,e. g. methyl, ethyl, npropyl, n-butyl, isobutyl, etc., R1 represents analkyl group, e. g. methyl, ethyl, n-propyl, isopropyl, n-butyl,isobutyl, etc., R2 and R3 each represents a hydrogen atom or amethylgroup, R2 and R3 always being diiierent, D represents analkoxy-o-naphthylene group, and X represents the bromide or the iodideanion.

The hydrobromic acid employed advantageously contains from 35 to 48 percent by weight of hydrogen bromide, the remainder, of course, beingwater. Constant boiling hydrobromic acid, 1. e. the48 per cent, is mostadvantageously employed. The hydrolysis is carried out mostadvantageously by refluxing the mixture of hydrobromic acid and alkoxycyclammonium alkobromide or alkiodide. However, higher or lowertemperatures canbe used, e. g. temperatures from to C.

The hydrolysis product is a hydroXy cyclammonium alkobromide and this insome cases is advantageously converted to the cyclammonium alkiodide bytreating a solution of the hydrolysis product with an aqueous oralcoholic solution of a water-soluble metal iodide, e. g. an alkalimetal iodide, e. g. sodium or potassium iodide. The hydroxy cyclammoniumalkiodide can be converted to the hydroxy cyclammonium alkochloride byheating the hydroxy cyclammonium alkiodide with a suspension of silverchloride in methyl alcohol, or with a suspension of silver chloride in aphenol, according to the process described in United States Patent2,245,249, dated June 10, 1941. The alkobromide can be regenerated fromthe alkochloride by treating a solution ofthe alkochloride with aconcentrated aqueous solution of sodium or potassium bromide.

The following examples will serve to illustrate further the manner ofpracticing our invention.

Example 1.6-hydromyquinalcline ethioclzde 49.4 g. of G-methoxyquinaldineethiodide were refluxed for three hours with 75 cc., 48 per centhydrobromic acid. The brown solution was chilled and the solid whichseparated was filtered oil. It was dissolved in 200 cc. of ethyl alcoholand to the hot solution was added a solution of 33.8 g. sodium iodide ina minimum of ethyl alcohol. The resulting solution was cooled, the solidwas filtered off. It was washed with a small amount of cold ethylalcohol and dried. A yield of 35.2 g., 74 per cent was obtained. Meltingpoint 257-450 C. with decomposition-tan crystals.

Example 2.7hydro:cyquinaldine methobromide 15.75 grams of'l-methoxyquinaldine methiodide and 35 cc. of 43 per cent hydrobromicacid were mixed in a 200 cc. flask and refluxed for 1 hours. Thereaction mixture was chilled to C. On stirring, it set to a solid mass.It was chilled again to 0 C. and then filtered, washed with acetone anddried. A yield of 9.2 grams of colorless material was obtained.

Example 3.7hydroa:yquinaldine ethobromide NfCH 16.5 grams of7-methoxyquinaldine ethiodide and 30 cc. of 48 per cent hydrobromic acidwere mixed in a 200 cc. flask and refluxed 1 /2 hours. The solution waschilled to 0 C. and diluted with 3.volumes of acetone and chilled for 2hours at 0 C. The separated solid was filtered off, washed with acetoneand dried. A yield of 9.8 grams of colorless material was obtained.

. Example 4.6-hydr0ryle31idine methobromide 4 Example5.--6-hydro:cylepidine ethob'romide (lg H5 B1 grams of G-methoxylepidineethiodide and cc. of 48 per cent hydrobromic acid were mixed in a 200cc. flask and refluxed 1 hour. The reaction mixture was cooled to roomtemperature and 250 cc. of acetone added and the mixture chilled to 0 C.The separated solid was filtered off, washed with acetone and dried. Ayield of 19.3 grams of colorless material was obtained.

Example 6.5 hydroxy 2,3,3 trimethylindolenine methiodide CH3 I 33.1grams of 5-methoxy-2,3,3trimethylindolenine methiodide and cc. of 48 percent hydrobromic acid were mixed in a 200 cc. flask and refluxed 1hours. The reaction mixture was chilled to 0 C. and the separated solidwasfiltered as dry as possible. The wet material is dissolved in ethylalcohol and treated with a hot solution of 15 grams of sodium iodide inethyl alcohol. The mixture was chilled to 0 C. and the separated solidwas filtered ofi and dried. A yield of 16.5 grams of colorless solid wasobtained of melting point 271--272 0. with decomposition.

Example 7.--5-hydrory-2,3,3-trimethylindolenine ethiodide CH CH3 a s I34.5 grams of 5-methoxy-2,3,3trimethylindolenine ethiodide and 60 cc. of48 per cent hydrobromic acid were mixed in a 200 cc. flask and refluxed1 hours. The solution was chilled to 0 C. and stirred to preventsupercooling. The separated solid was filtered as dry as possible. Thecrude material was dissolved in 200 cc. ethyl alcohol in the hot andtreated with 15 grams. of sodium iodide. Some solid separatedimmediately and was filtered ofi. The filtrate was chilled to 0 C. Thesolid which separated was filtered off and dried. A yield of 17.5 gramsof colorless solid of melting point 210-213 C. with decomposition wasobtained.

Earample 8.5-hydro:vy-2-methylnaphtho[1,2]

thiazole methobro'mz'de 17.5 grams of 5-methoxy-2-methyl naphtha-[1,2lthiazole methiodide and 30 cc. of 48 per cent hydrobromic acid weremixed in a 200 cc. flask and refluxed 1 hours. The reaction mixture waschilled and the solid which separated was filtered ofi and washed withacetone and dried. A yield of grams of colorless material was obtained.

Example 9.5-hydroa:y-Z-methylnaphtho[1,2]

' thz'azole ethobromide 14.2 grams of 5-methoxy-2-methyl naphtha-[1,2]thiazole ethiodide and cc. of 48 per centhydrobromic acid weremixed in a 200 cc. flask and refluxed 2 hours. chilled to 0 C. and. theseparated solid was filtered off, washed lightly with water and dried. Ayield of 12 grams of colorless solid was obtained.

In a manner similar to that illustrated in Example 1,5-hydroxyquinaldine ethiodide can be prepared by replacing the6-methoxyquinaldine ethiodide with a molecularly equivalent amount of5-ethoxyquinaldine ethiodide, S-hydroxyquinaldine n-propiodide can beprepared by replacing the G-methoxyquinaldine ethiodide with then-propiodide, G-hydroxyquinaldine n-butiodide can be prepared byreplacing the 6-methoxyquinaldine ethiodide with the n-butobromide, etc.

The alkoxy cyclammonium quaternary salts which we employ in our processcan be prepared by heating the corresponding alkoxy heterocyclicnitrogen bases with an alkyl bromide or alkyl iodide, e. g. methyliodide, ethyl iodide, n-propyl iodide, n-butyl bromide, n-propylbromide, isobutyl bromide, n-butyl iodide, etc., using a closed tubewhere higher temperatures are desired or the volatility of the reactantsdemands.

The alkoxy heterocyclic nitrogen bases are known in several instances,dines can be prepared by the interaction of an alkoxyaniline withparaldehyde (or aldol) nitrobenzene and sulfuric acid, according to theprocess given by Doebner and Miller, Ber. 16, 2465 (1886) dine gives6-methoxyquinaldine. See also Braunholtz, J. Chem. Soc. 121, 169 (1922).The alkoxylepidines can be prepared by heating an alkoxyaniline withmethyl vinyl ketone, Campbell et al., J. Am. Chem. Soc. 67, 86 (1945).5-alk0xy- Z-methylnaphtho[1,2lthiazoles are described in British Patent593,025, complete accepted October '7, 1947.8-a1koxyl-2-methylnaphtho[1,2lthiazoles are described in British Patent411,479, accepted June 5, 1934. Alkoxy-2,3,3-trimethylindolenines can beprepared by heating an alkoxyphenylhydrazine with methyl isopropylketone and refluxing the resulting mixture with glacial acetic acid. Thefollowing example will serve to illustrate further the preparation ofthe alkoxy- 2,3,3-trimethylindolenines.

Example 10.5-methozny-2,3,3-trimethylindolenine CH CH3 c omo- C-GH:

The reaction mixture was The alkoxyquinal- Thus p-methoxyaniline(p-anisii 33.8 grams of p-methoxyphenylhydrazine and 23.3 grams ofmethylisopropyl ketone were mixed in a 200 cc. flask and warmed on asteam bath until water was formed as shown by the appearance of waterdroplets. cc. of glacial acetic acid was then added and the solution wasrefluxed 3 hours. The solvent was removed under reduced pressure on asteam bath and the residue taken up in dilute hydrochloric acid (240cc.'of about 6 per cent hydrochloric acid). The solution was filteredand the filtrate was made alkaline with sodium carbonate solution. Theoil was extracted with diethyl ether, the ether solution dried withpotassium carbonate and the ether removed on a'steam bath. The residuewas distilled under reduced pressure. Boiling point -145/mm. A yield of20.6 grams was obtained which was 40 per cent of the theoretical.

The hydroxy cyclammonium alkohalides of our invention can be employed toprepare cyanine, styryl and merocyanine dyes. Thus, the hydroxycyclammonium alkohalides can be condensed with cyclammonium alkylquaternary salts containing an iodine atom or a thioether group in areactive position (i. e. the aor 'y-position) to give monomethinecyanine dyes containin a hydroxyl group. The condensations areadvantageously effected in the presence of a basic condensing agent, e.g. a tertiary amine, e. g. a trialkylamine, such as triethylamine,trin-propylamine, triisoamylamine, N-methylpiperidine,N-ethylpiperidine, etc. Typical cyclammonium alkyl quaternary saltscontaining an iodine atom or thioether group are: 2-iodoquinolineethiodide, 2-iodoquinoline n-butiodide, 2 methylmercaptobenzothiazolemetho ptoluenesulfonate, 2 methylbenzoxazole etho ptoluenesulfonate,2-methylmercapto c-naphthothiazole etho-p-toluenesulfonate, etc.

The hydroxy cyclammonium alkohalides can be condensed with alkylorthocarboxylates, e. g. ethyl orthoformate, ethyl orthoacetate, ethylorthoproprionate methyl orthoformate, etc., in pyridine, to givesymmetrical carbocyanine dyes.

The hydroxy cyclammonium alkohalides can be condensed with cyclammonium'quaternary salts containing, in a reactive position, a fi-arylaminovinylor a p-acylated arylaminovinyl group to give unsymmetrical carbocyaninedyes. The condensations are advantageously effected in the presence of abasic condensing agent, e. g. the tertiary amines set forth above.Typical cyclammonium quaternary salts containing a p-arylaminovinyl orc-acylated arylaminovinyl group are: {3 acetanilidovinylbenzoxazoleethiodide, li-anilinovinylthiazoline methiodide,fl-acetanilidovinylbenzothiazole ethiodide, 4 ([3 anilinevinyl)quinoline n-butiodide, 2 [2 (N methylanilino) vinyllbenzothlazoleethiodide, 2 fi acetanilidovinyl-4-methylthiazo1e ethiodide, etc.

The hydroxycyclammonium alkohalides can be condensed withB-anilinoacrolein anilhydrochloride or with glutaconic dianilidehydrochloride, in the presence of a basic condensing agent, e. g. atertiary amine, e. g. those set forth above, to give diandtricarbocyanine dyes.

The hydroxy cyclammonium alkohalides can be condensed with heterocycliccompounds containing a, ketomethylene group (CHz-CO) and alkylorthocarboxylates, e. g. ethyl orthoformate, ethyl orthoacetate, ethylorthopropionate, etc., in the presence of pyridine, to givemercarbocyanine dyes. Typical ketomethylene compounds include rhodanine,3-ethylrhodanine, 3-;8-hydroxyethylrhodanine, 3-phenylrhodanine,

3 ethyl 2,4(3,5) oxazoledione, 1 methyl- 3 *phenyl pyrazolone, 3 ,3carboxyethylrhodanine, 3 p carboxyphenylrhodanine, 3 carboxymethyl2,4(3,5) orazoledione, 1 methyl 3 p sulfophenyl 5 pyrazolone, 1,3diphenyl 2 thiohydantoin, 1 ethyl 3- phenyl 2 thiohydantoin, lcarboxymethyl- 3 phenyl 2 thiohydantoin, 3 p sulfoethylrhodanine, etc.

The hydroxy cyclammonium alkohalides can be condensed with heterocycliccompounds containing, substituted on the methylene group, an acylatedarylaminomethylene group, e. g. 5-acetanilidomethylenerhodanines, 5acetanilidomethylene 2 thiohydantoins, 5 acetanilidomethylene 9 thio 2,l(3,5) -oxazolediones, etc., in the presence of a basic condensingagent, e. g. the tertiary amines set forth above.

The hydroxy cyclammonium alkohalides can be condensed withdialkylaminobenzaldehydes, e. g. p-dimethylaminobenzaldehyde,p-diethylaminobenzaldehyde, etc. to give styryl dyes. The condensationsare advantageously carried out in the presence of a secondary amine, e.g. piperidine, methylpiperidines, etc.

The hydroxy cyclammonium alkohalides can be condensed with pyrrolecarboxaldehydes to give pyrrolocarbocyanine dyes. The condensations areadvantageously carried out in a solvent, e. g. methyl, ethyl, n-propyl,isopropyl, isobutyl or n-butyl alcohol. Pyrrole carboxaldehydes can beprepared by the method of Nenitzescu and Isacescu, Bull. soc. chim.Romania 11, 135 (1929). See also Brooker and Sprague, J. Am. Chem. Soc.67, 1869 (1945).

The hereindescribed cyanine, merocyanine and styryl dyes sensitizephotographic silver halide emulsions, especially the customarilyemployed gelatino-silver-chloride, chlorobromide, chlorobromoiodide,bromide and bromoiodide emulsions, when incorporated therein, e. g. in aconcentration of from 10 to 40 mg. per liter of emulsion. The dyes canbe added to the emulsions from their solutions in methyl alcohol. Thepyrrolocyanine dyes described herein can be employed for the preparationof overcoating layers, filter layers and anti-halation layers forphotographic elements.

Among the dyes that have been prepared from the hereindescribedhydroxycyclammonium salts are 6,6' dihydroxy 3,3 dimethyl 4,5,4,5'dibenzothiacarbocyanine bromide, fine dark crystals, M. P. greater than300 C.

3,3 diethyl 6,6 dihydroxy 4,5,4,5 dibenzothiacarbocyanine bromide, veryfine dark crystals, melting with slow decomposition from 285 0.

6,6 dihydroxy 3,3 .imethyl 9 ethyl 4,5,425-dibenzothiacarbocyaninebromide, fine dark crystals, melting from 275 C. with slowdecomposition.

5,5 dihydroxy l,3,3,1,3,3' hexamethylindo- 'carbocyanine iodide, stoutgreen needles with bright reflex, M. P. greater than 325 C.

4 [(5 hydroxy 1,3,3 trimethylindolylidene) ethylidenel 3 methyl l phenyl4(5) pyrazolone, orange crystals with bright reflex, M. P. 321-322 C.with decomposition.

7,7 dihydroxy 1,1 dimethyl 2,2 carbocyanine iodide, very dark-greencrystals, M. P. 323-.324" 'C. with decomposition.

1,1 diethyl 7,7 dihydroxy 2,2 carbocyanine iodide, fine blue-greenpowder, M. P.

'315-316" C. with decomposition.

1,1 diethyl 7 hydroxy 2,2 cyanine iodide, fine dark red cubes, M. P. 277to 280 C. with decomposition.

3 ethyl 5 [(3 ethyl 5 hydroxyquinolylidene) ethylidenelrhodanine, purplecrystals, M. P. 312-313 C. with decomposition.

6,6 dihydroxy 1,1 dimethyl 4,4 carbocyanine bromide, very fine darkpowder, M. P. 275-276" C. with decomposition.

1,1 diethyl 6,6 dihydroxy 4,4 carbocyanine bromide, very fine greenpowder, M. P. 267-268" C., with decomposition.

What we claim as our invention and desire to be secured by LettersPatent of the United States 1. A process for preparing a hydroxycyclammonium quaternary salt comprising hydrolyzing at a temperature offrom to C., in the presence of hydrobromic acid, an alkoxy Cyclammoniumsalt selected from the group consisting of those represented by thefollowing general formula:

and

C-CHa and s D CCHa wherein R represents an alkyl group, R1 represents analkyl group, R2 and R3 each represents a member selected from the groupconsisting of a hydrogen atom and a methyl group, R2 and R3 always beingdifferent, D represents an alkoxy-onaphthylene group, and X represents anumber selected from the group consisting of the bromide and the iodideanion.

2. A process for preparing a hydroxy cyclammonium quaternary saltcomprising hydrolyzing at a temperature of from 80 to 150 C., in thepresence of hydrobromic acid, an alkoxy cyclammonium salt selected fromthe group consisting of those represented by the following generalformula:

wherein R representsd a primary alkyl group of the formula CnI-I2n+1wherein n represents a positive integer of from 1 to 4;, R1 representsan alkyl group of the formula. CnH2n+1 wherein 71 presents a positiveinteger of from 1 to 2, and R2. and R3 each represents a member selectedfrom the group consisting of a hydrogen atom and a methyl group, R2 andR3 always being different. I

3. A process for preparing a hydroxy cyclammonium quaternary saltcomprising hydrolyzing at a temperature of from 80 to 150 C., in thepresence of hydrobromic acid, an alkoxy cyclammonium quaternary saltselected from the group consisting of those represented by the followinggeneral formula:

mom

CH N/ s R I wherein R represents a primary alkyl group of the formulaC'nHznH wherein n represents a positive integer of from 1 to 4, and R1represents a positive integer of the formula CnH2n+l wherein nrepresents a positive integer of from 1 to 2.

4. A process for preparing a hydroxyquinaldine quaternary saltcomprising hydrolyzing at a temperature of from 80 to 150 C., in thepresence of constant boiling hydrobromic acid, fi-methoxyquinaldineethiodide.

5. A process for preparing a hydroxy cyclammonium quaternary saltcomprising hydrolyzing at a temperature of from 80 to 150 C., in thepresence of hydrobromic acid, an alkoxy cyclammonium quaternary saltselected from the group consisting of those represented by the followinggeneral formula:

wherein D represents an alkoxy-o-naphthylene group, and R represents aprimary alkyl group of the formula CnH2n+1 wherein n represents apositive integer of from 1 to 4.

6. A process for preparing a hydroxynaphthothiazole quaternary saltcomprising hydrolyzing at a temperature of from 80 to 150 C., in thepresence of constant boiling hydrobromic acid, 5-methoxy-2-methylnaphtha[1,2] thiazole ethiodide.

7. A process for preparing hydroxy cyolam- N R/ \I wherein R representsa primary alkyl group of the formula CnH2n+1 wherein n represents a,positive integer of from 1 to 4 and R1 represents an alky group of theformula CnH2n+1 wherein n represents a positive integer of from 1 to 2.

8. A process for preparing a hydroxy-2,3,3- trimethylindoleninequaternary salt comprising hydrolyzing at a temperature of from to C.,in the presence of constant boiling hydrobromic acid,5-methoxy-2,3,3-trimethylinclolenine ethioclide.

EARL J. VAN LARE. LESLIE G. S. BROOKEER.

REFERENCES CITED The following references are of record in the file ofthis patent:

UNITED STATES PATENTS Number Name Date 2,394,069 Kendall et al Feb. 5,1946 2,332,517 Kendall Oct. 26, 1943 OTHER REFERENCES Braunholtz: J.Chem. Soc. (London), vol. 121, pp. 169173 (1922).

Small et al.: Chemistry of the Opium Alkaloids (U. S. Govt. PrintingOfilce, 1932), pp. 2 and 3.

Beilstein: Handbuch der Organischen Chemie (4th ed., 1935), vol. 21, p.104.

Fieser et al.: Organic Chemistry (D. C. Heath and Co., Boston, 1944), p.142.

P. B. Report 17,677 Frame 104, published January 30, 1948.

1. A PROCESS FOR PREPARING A HYDROXY CYCLAMMONIUM QUATERNARY SALTCOMPRISING HYDROLYZING AT A TEMPERATURE OF FROM 80* TO 150* C., IN THEPRESENCE OF HYDROBROMIC ACID, AN ALKOXY CYCLAMMONIUM SALT SELECTED FROMTHE GROUP CONSISTING OF THOSE REPRESENTED BY THE FOLLOWING GENERALFORMULA: